TY - JOUR
T1 - Upregulation of neuronal nicotinic receptor subunits α4, β2, and α7 in transgenic mice overexpressing human acetylcholinesterase
AU - Svedberg, Marie M.
AU - Svensson, Anne Lie
AU - Johnson, Mary
AU - Lee, Mandy
AU - Cohen, Osnat
AU - Court, Jennifer
AU - Soreq, Hermona
AU - Perry, Elaine
AU - Nordberg, Agneta
PY - 2002
Y1 - 2002
N2 - Neuronal nicotinic receptor binding sites as well as mRNA levels encoding for subunits α4, β2, and α7 were analysed in 3-mo-old transgenic mice generated with a neuronal overexpression of human acetylcholinesterase and in age-matched controls. The acetylcholinesterase transgenic mice display progressive cognitive impairment in spatial learning and memory. We here report a significantly increased [3H]epibatidine and [125I]αbungarotoxin binding in the cortex and the caudate putamen of these mice. Quantitative in situ hybridization showed significant upregulation of mRNA corresponding to the nicotinic receptor subunits α4, β2, and α7 in various brain regions in the transgenic mice compared to nontransgenic controls. Our results suggest that disruption of balanced cholinergic transmission by constitutive overexpression of acetylcholinesterase is accompanied by variable upregulation of several nicotinic receptor subtypes, in particular these associated with cholinergic terminals participating in compensatory response.
AB - Neuronal nicotinic receptor binding sites as well as mRNA levels encoding for subunits α4, β2, and α7 were analysed in 3-mo-old transgenic mice generated with a neuronal overexpression of human acetylcholinesterase and in age-matched controls. The acetylcholinesterase transgenic mice display progressive cognitive impairment in spatial learning and memory. We here report a significantly increased [3H]epibatidine and [125I]αbungarotoxin binding in the cortex and the caudate putamen of these mice. Quantitative in situ hybridization showed significant upregulation of mRNA corresponding to the nicotinic receptor subunits α4, β2, and α7 in various brain regions in the transgenic mice compared to nontransgenic controls. Our results suggest that disruption of balanced cholinergic transmission by constitutive overexpression of acetylcholinesterase is accompanied by variable upregulation of several nicotinic receptor subtypes, in particular these associated with cholinergic terminals participating in compensatory response.
KW - Acetylcholinesterase
KW - Acetylcholinesterase overexpressing mice
KW - Binding sites
KW - Cholinergic receptor
KW - mRNA
KW - Nicotinic receptors
UR - http://www.scopus.com/inward/record.url?scp=0036014116&partnerID=8YFLogxK
U2 - 10.1385/JMN:18:3:211
DO - 10.1385/JMN:18:3:211
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C2 - 12059039
AN - SCOPUS:0036014116
SN - 0895-8696
VL - 18
SP - 211
EP - 222
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
IS - 3
ER -